tbuckley/cabot-search huggingface dataset:
Purine nucleoside phosphorylase enables dual metabolic checkpoints that prevent T cell immunodeficiency and TLR7-associated autoimmunity
Authors: Evan R. Abt, Khalid Rashid, Thuc M. Le, Suwen Li, Hailey R. Lee, Vincent Lok, Luyi Li, Amanda L. Creech, Amanda N. Labora, Hanna K. Mandl, Alex K. Lam, Arthur Cho, Valerie Rezek, Nanping Wu, Gabriel Abril-Rodriguez, Ethan W. Rosser, Steven D. Mittelman, Willy Hugo, Thomas Mehrling, Shanta Bantia, Antoni Ribas, Timothy R. Donahue, Gay M. Crooks, Ting-Ting Wu, Caius G. Radu
Journal: Journal of Clinical Investigation (2022)

Purine nucleoside phosphorylase (PNP) enables the breakdown and recycling of guanine nucleosides. PNP insufficiency in humans is paradoxically associated with both immunodeficiency and autoimmunity, but the mechanistic basis for these outcomes is incompletely understood. Here, we identify two immune lineage-dependent consequences of PNP inactivation dictated by distinct gene interactions. During T cell development, PNP inactivation is synthetically lethal with downregulation of the dNTP triphosphohydrolase SAMHD1. This interaction requires deoxycytidine kinase activity and is antagonized by microenvironmental deoxycytidine. In B lymphocytes and macrophages, PNP regulates Toll-like receptor 7 signaling by controlling the levels of its (deoxy)guanosine nucleoside ligands. Overriding this regulatory mechanism promotes germinal center formation in the absence of exogenous antigen and accelerates disease in a mouse model of autoimmunity. This work reveals that one purine metabolism gene protects against immunodeficiency and autoimmunity via independent mechanisms operating in distinct immune lineages and identifies PNP as a potentially novel metabolic immune checkpoint.
Selection and identification of a novel ssDNA aptamer targeting human skeletal muscle
Authors: Shuming Sun, Han Liu, Yan Hu, Yanpeng Wang, Mingri Zhao, Yijun Yuan, Yafei Han, Yingying Jing, Jin Cui, Xiaoxiang Ren, Xiao Chen, Jiacan Su
Journal: Bioactive Materials (2022)

Skeletal muscle disorders have posed great threats to health. Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging. Aptamers can improve targeting efficacy. In this study, for the first time, the human skeletal muscle-specific ssDNA aptamers (HSM01, etc.) were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment (SELEX). The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells
Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial
Authors: Guylaine Labro, Florence Tubach, Lisa Belin, Jean-Louis Dubost, David Osman, Grégoire Muller, Jean-Pierre Quenot, Daniel Da Silva, Jonathan Zarka, Matthieu Turpin, Julien Mayaux, Christian Lamer, Denis Doyen, Guillaume Chevrel, Gaétan Plantefeve, Sophie Demeret, Gaël Piton, Cyril Manzon, Evelina Ochin, Raphael Gaillard, Bertrand Dautzenberg, Mathieu Baldacini, Said Lebbah, Makoto Miyara, Marc Pineton de Chambrun, Zahir Amoura, Alain Combes, Jessica Palmyre, Linda Gimeno, Assitan Kone, Cedric Vialette, Ouramdane Slimi, Juliette Chommeloux, Lucie Lefevre, Matthieu Schmidt, Guillaume Hekimian, Charles-Edouard Luyt, Laure Stiel, Anne-Florence Dureau, Kuteifan Khaldoun, Hanna Eid, Matthieu Baldacini, Cecile Zyberfajn, Julien Manson, Nathanael Charrier, Angelique Balabanian, Damien Contou, Olivier Pajot, Megan Fraisse, Paul Desaint, Florence Sarfati, Muriel Fartoukh, Guillaume Voirot, Alexandre Elabbabi, Michel Djibre, Cyrielle Desnos, Pierre Garcon, Ly van Vong, Andrea Issad, Bertrand Pillot, Delphine Reither, Patrick Rouge, Pascale Foliot, Lynda Bendjamar, Valentin Pointurier, Hadrien Winiszewski, Gilles Capellier, Jean-Christophe Navellou, Romain Tapponnier, Emilie Panicucci, Lucas Morand, Jean Dellamonica, Clement Saccheri, Nicolas Weiss, Clemence Marois, Loic Le Guennec, Benjamin Rohaut, Luis Ensenat, Cecilia Billiou, Maria Aroca, Marie Baron, Alexandre Demoule, Alexandra Beurton, Come Bureau, Maxens Decavele, Martin Dres, Frederique Bayle, Quoc Viet Le, Lionel Liron, Jean-Baptiste Putegnat, Francois Salord, Pascal Andreu, Hakim Slimani, Baptiste Roudeau, Marie Labruyere, Marine Jacquier, Nadia Anguel, Soufia Ayed, Edgard Durand, Laurent Guerin, Christopher Lai, Jerome Aboab, Sophie Alviset, Laurent Laine, Mathilde Azzi, Tazime Issoufaly, Laurent Tric, Lyes Knani, Chahrazad Bey Boumezrag, Nicolas Viault, Francois Barbier, Thierry Boulain, Toufik Kamel, Mai-Anh Nay, Sophie Tollec, An Hung Nguyen
Journal: Intensive Care Medicine (2022)
Where is your lactation room? Lactation policies and practices in oncology trainee and early career physicians.
Authors: Sindhu Janarthanam Malapati, Sunny R K Singh, Dame Idossa, Ximena Jordan Bruno, Fumiko Chino, Monica Arun Patel, Zihan Wei, Narjust Duma
Journal: Journal of Clinical Oncology (2022)

11054 Background: Training and early career years coincide with childbearing and raising young families, which places increased demands on new parents. With increasing numbers of female oncologists in the workforce, there is a need to assess and amend current workplace lactation policies. We surveyed Medical and Radiation Oncology trainees and early career faculty to assess policies and practices regarding lactation during training and early career. Methods: An anonymous 48 question cross-sectional survey developed by researchers with expertise in gender equity was distributed via email and social media channels between May and June 2021 to oncology trainees and physicians within 5 years of terminal training; program directors (PDs) were surveyed separately. Descriptive statistics were used. Results: Of the 255 complete responses, 26% (65) respondents breastfed for any length of time upon return to work. Of these, 54% (35) were trainees and 46% (30) early career faculty. 69% (45) had access to a designated lactation room; however, 57% (37) noted that duration of their pumping breaks was inadequate to access and use the lactation room. Most (60%, 39) did not feel comfortable asking for protected time to pump. Employment contracts did not specifically include pumping breaks for 66% (43), while 34% (22) were unsure about their contract policies surrounding lactation. Of all breastfeeding mothers, 77% (50) felt their colleagues to be supportive of their needs; a minority reported negative responses due to pumping breaks from faculty (11%), co-fellows/colleagues (8%) and clinic staff (15%). 51% (33) bought a wearable pump prior to return to work, of which 70% (23) found it financially burdensome. Most common reasons for buying a wearable pump were to improve efficiency during work hours (61%, 20) and lack of adequate pumping breaks (39%, 13). Among 23 PDs who responded to the survey, 65% (15) had a program policy regarding lactating trainees, 9% (2) blocked clinic appointments to allow pumping breaks, 91% (21) provided lactation rooms, 83% (19) reported the lactation rooms are easily accessible. Conclusions: Both infrastructure and time accommodations made for the lactating parent are inadequate. There is a disconnect between the trainee and PDs’ perception of provided accommodations. Systemic changes that provide adequate time and space for lactation to busy clinicians and trainees is imperative to ensure retention of women oncologists in the workforce.
A systematic review and meta-analysis to evaluate the efficacy and safety of nivolumab for advanced esophageal, gastroesophageal, and gastric cancer.
Authors: Mosunmoluwa Oyenuga, Mohamed G Mohamed, Sara Sartaj, Rushin Patel, Alexandre Lacasse, Mudresh Mehta, Sandeep Sen
Journal: Journal of Clinical Oncology (2022)

e16060 Background: Esophageal, gastroesophageal, and gastric cancers make up about 1% of the cancer cases in the United States and most patients are diagnosed at advanced stages. Despite treatment options available, these patients have a median survival of about one year. Due to the advancement in treatment using immune checkpoint inhibitors in cancer therapy, this class of medications were recently approved for their use in patients with esophageal, gastroesophageal, and gastric cancer. A literature review and meta-analysis was conducted to evaluate the efficacy and safety of use of nivolumab in these group of patients. Methods: We systematically searched multiple databases using pre-specified search terms. We included only RCTs comparing Nivolumab with/without chemotherapy versus chemotherapy, in patients with advanced esophageal, gastroesophageal, or gastric cancer. Co-primary outcomes were overall survival (OS) and progression free survival (PFS). We also reported response rates, sensitivity analysis and adverse effects (AE), using fixed effects model via RevMan 5.4 software. Results: Three RCTs were included with a total of 2,645 patient and a median follow-up of 13 months. The patients’ mean age was 62±22 years, 75% were males, 79% were stage IV metastatic disease, and 29% had ≥1% PD-L1 expression. Compared to the chemotherapy group, Nivolumab group had a significantly favorable OS and PFS [HR 0.78;95% CI (0.69, 0.87), P &lt; 0.001], [HR 0.83;95% CI (0.75, 0.92), P &lt; 0.001] respectively. Sensitivity analysis showed significant effect of Nivolumab only in patients with ≥1 % PD L1 expression [HR 0.71; 95% CI (0.64, 0.80), P &lt; 0.001]. Chemotherapy group had a significantly favorable outcome regarding serious AE [OR 1.57;95% CI (1.28, 1.93), P &lt; 0.001], and diarrhea [OR 1.29;95% CI (1.07, 1.56), P = 0.007], with no difference regarding AE leading to death [OR 1.75;95% CI (0.88, 3.47), P = 0.11]. Conclusions: The use of nivolumab in patients with advanced esophageal, gastroesophageal, and gastric cancers is associated with improved disease-free survival and overall survival compared to treatment with chemotherapy, albeit at an increased risk of serious adverse effects. The improvement in survival was significant in patients with ≥1% PD L1 expression.
Blending with transition metals improves bioresorbable zinc as better medical implants
Authors: Yingchao Su, Jiayin Fu, Juncen Zhou, Elias Georgas, Shaokang Du, Yi-Xian Qin, Yadong Wang, Yufeng Zheng, Donghui Zhu
Journal: Bioactive Materials (2022)

Zinc (Zn) is a new class of bioresorbable metal that has potential for cardiovascular stent material, orthopedic implants, wound closure devices, etc. However, pure Zn is not ideal for these applications due to its low mechanical strength and localized degradation behavior. Alloying is the most common/effective way to overcome this limitation. Still, the choice of alloying element is crucial to ensure the resulting alloy possesses sufficient mechanical strength, suitable degradation rate, and acceptable biocompatibility. Hereby, we proposed to blend selective transition metals (i.e., vanadium-V, chromium-Cr, and zirconium-Zr) to improve Zn's properties. These selected transition metals have similar properties to Zn and thus are beneficial for the metallurgy process and mechanical property. Furthermore, the biosafety of these elements is of less concern as they all have been used as regulatory approved medical implants or a component of an implant such as Ti6Al4V, CoCr, or Zr-based dental implants. Our study showed the first evidence that blending with transition metals V, Cr, or Zr can improve Zn's properties as bioresorbable medical implants. In addition, three in vivo implantation models were explored in rats: subcutaneous, aorta, and femoral implantations, to target the potential clinical applications of bioresorbable Zn implants.
Association of depth of target lesion response to brigatinib with outcomes in patients with ALK inhibitor-naive <i>ALK+</i> NSCLC in ALTA-1L.
Authors: D. Ross Camidge, Hye Ryun Kim, Myung-Ju Ahn, James Chih-Hsin Yang, Ji-Youn Han, Maximilian Hochmair, Ki Hyeong Lee, Angelo Delmonte, Rosario Garcia Campelo, Dong-Wan Kim, Frank Griesinger, Enriqueta Felip, Raffaele Califano, Alexander I. Spira, Michael Thomas, Scott N. Gettinger, Marcello Tiseo, Yuyin Liu, Pingkuan Zhang, Sanjay Popat
Journal: Journal of Clinical Oncology (2022)

9072 Background: In patients (pts) with crizotinib (CRZ)-refractory advanced ALK+ NSCLC in the phase 2 ALTA trial (NCT02094573), the depth of target lesion response to brigatinib (BRG) correlated with PFS and OS. Here, we examine the association of maximum decrease in target lesions with PFS and OS in ALTA-1L (NCT02737501), a randomized phase 3 trial of BRG vs CRZ in pts with ALK inhibitor-naive advanced ALK+ NSCLC. Methods: Pts were randomized 1:1 to receive BRG 180 mg qd (7-day lead-in at 90 mg; n=137) or CRZ 250 mg bid (n=138). Pts with target lesion assessment by blinded independent review committee (BIRC) were grouped based on greatest decrease from baseline per RECIST v1.1: none–50%, 51%–75%, and 76%–100% shrinkage. Outcomes in the ≤50% target lesion shrinkage group served as the comparator for outcomes in the 51%–75% and 76%–100% groups. Results: At study end (last pt contact: Jan 29, 2021), 124/137 pts in the BRG arm and 125/138 pts in the CRZ arm had ≥1 evaluable target lesion assessment; female (BRG/CRZ), 51%/59%; median age, 57.5/60.0 years. Median follow-up was 40.8/15.7 months. In BRG/CRZ arms, 76%-100% shrinkage was observed in 56%/34% of pts, 51%-75% shrinkage in 27%/30%, and ≤50% shrinkage in 16%/35%, respectively. BRG was associated with significantly more pts with target lesion shrinkage &gt;75% vs CRZ ( P=0.0005), and a Cochran-Armitage trend analysis demonstrated significantly deeper response across all shrinkage groups for BRG compared with CRZ ( P&lt;0.0001). A majority of pts in the BRG arm experienced 76%–100% target lesion shrinkage in all subgroups analyzed. Pts treated with BRG or CRZ with target lesion shrinkage &gt;50% had lower risk of a PFS event (BRG HR [95% CI]: 51%–75% shrinkage, 0.58 [0.29–1.18]; 76%–100%, 0.23 [0.12–0.46]; CRZ: 51%–75% shrinkage, 0.68 [0.41–1.12]; 76%–100%, 0.26 [0.15–0.45]) or an OS event (BRG: 51%–75% shrinkage, 0.39 [0.17–0.89]; 76%–100%, 0.15 [0.07–0.35]; CRZ: 51%–75% shrinkage, 0.43 [0.21–0.85]; 76%–100%, 0.23 [0.10–0.50]) than pts with ≤50% shrinkage. Longer median time to PFS and OS and higher 4-year estimated OS rates were associated with depth of response in both arms (Table). Conclusions: In this exploratory post hoc analysis, BRG demonstrated significantly deeper target lesion response vs CRZ. Pts with &gt;75% shrinkage had significantly reduced risk of a PFS or OS event vs pts with ≤50% target lesion shrinkage. Clinical trial information: NCT02737501. [Table: see text]
Covid 19 infection leading to a subsequent new primary cancer diagnosis, Real-world data (RWD) analysis on members of Belong.life, a global cancer application (app).
Authors: Daniel A. Vorobiof, Bozhena Haikin, Alon Litvin, Irad Deutsch, Eliran Malki
Journal: Journal of Clinical Oncology (2022)

e18775 Background: Some known viral infections can lead to a diagnosis of cancer (e.g: HPV, HIV, EBV, etc.) Anecdotical reports of a Covid 19 infection, and the subsequent diagnosis of a new cancer have been mentioned by few patients (pts). This relationship has not yet been fully documented. Covid 19 infected persons have been identified to have a suppressed adaptive immunity, which one of its principal functions is to maintain occult cancer cells in an equilibrium state. We studied the possible role of a Covid 19 infection and the subsequent diagnosis of a new primary cancer happening during the Covid pandemic (01/2020 – 12/2021). A survey was sent to all new members of Belong.life, a free and anonymous global cancer app for pts and their caregivers. This study took place prior to the omicron variant surge. Methods: 2579 Belong.life members received randomly, in the app various cancer groups, a 10 questions voluntary survey regarding the onset of a Covid 19 infection and the development of a subsequent new primary cancer diagnosis. 262 replied of whom 124 fulfilled the eligibility criteria and confirmed having had a Covid 19 infection followed by a new cancer diagnosis. Data on the 124 pts was analyzed by Belong analysts, according to age, sex, geographical distribution, Covid 19 infection onset and type and timing of the cancer diagnosis. Results: Most pts were USA based (102/124, 82%), and 1/3 were &lt; 49 years, followed by a 1/3 in the 50-59 and &gt; 60 groups. 71% (88/124) were females. All had a prior Covid 19 infection and only 14 (11%) required hospitalization. 109/124 (88%) had a primary cancer diagnosis and 15 (12%) had disease recurrence. Breast cancer was diagnosed in 38% (47/124), followed by lung and gynecological cancers (10/124, 8% respectively). Time from Covid 19 infection to primary cancer diagnosis was &lt; 6 months in 57 /124 (46%) and 6-12 months in 40/124 (32%). Breast cancer developed earlier (&lt; 12 months) in 87% of the pts. In total 97/124 (78%) pts had their disease diagnosed within less than a year. Conclusions: Known viruses might precede the onset of a new cancer. The role of corona viruses and subsequent development of a cancer is unknown. Adaptive immunity maintains occult cancer cells in a steady state, while a Covid 19 infection interferes with it, causing a weak and delayed immune response, which could be responsible, after a period, for the onset of a new primary cancer. We are presenting RWD on 124 pts with new primary cancers diagnosed after a Covid 19 infection. This represents a 5% incidence in a random pts group (124/2579) as described above. Further studies should be planned to investigate this real world increased incidence and testing of the diverse immune parameters are also warranted to further understand the intersection pathways of Covid 19 infection and cancer development.
Validation of the recommended size cut-off for thermal ablation in T1 renal cell carcinoma patients, according to the EAU Guidelines
Authors: S. Luzzago, F.A. Mistretta, G. Mauri, R. Bianchi, A. Cioffi, D. Bottero, O. Blezien, L.M.I. Jannello, G. Marvaso, M. Ferro, D.V. Matei, B.A. Jereczek Fossa, F. Orsi, G. Musi, O. De Cobelli
Journal: European Urology (2022)
Introducing the Synchroseal: A new robotic setting for robot-assisted radical prostatectomy and super-extended lymph node dissection for locally advanced prostate cancer
Authors: L. Sarchi, C.A. Bravi, A. Mottaran, P. Piazza, S. Knipper, M. Paciotti, M. Amato, R. Farinha, F. Gonzalez Meza, M.A. Corsetti, C. Sinatti, S. Puliatti, R. De Groote, A. Mottrie
Journal: European Urology (2022)
Interventions for head and neck cancer survivors: A systematic review.
Authors: Danielle Nina Margalit, Talya Salz, Rebecca L. Venchiarutti, Kristi Milley, Mairead McNamara, Sophie Chima, Paige Druce, Larissa Nekhlyudov
Journal: Journal of Clinical Oncology (2022)

e24042 Background: Quality survivorship care includes cancer-related and general health care domains, including cancer surveillance and prevention of new cancers, management of psychosocial and physical late effects, health promotion/disease prevention, and management of chronic conditions. Survivors of head and neck cancer (HNC) have particularly complex unmet needs across all of these domains. We systematically reviewed interventions for HNC survivors to identify existing evidence and gaps in HNC survivorship care research. Methods: We performed a systemic review (PROSPERO ID: CRD42021269566) using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched MEDLINE, Embase, Emcare and PsycINFO for primary studies published in English between 2000 and 2021 to identify prospective studies for which interventions began after completion of cancer treatment and had a study endpoint ≥1 year after treatment completion. The population included adults treated with for HNC We used Covidence systematic review software to facilitate article screening and study selection. Two reviewers independently screened titles and abstracts followed by full texts for eligibility. Disagreements were resolved by consensus. Two reviewers critically appraised each selected study. Reviewers evaluated risk of bias with the Cochrane RoB 2.0 tool for randomized trials and the ROBINS-I tool for non-randomized studies. Due to the anticipated heterogeneity of included studies, narrative synthesis was used to summarize data. Results: The literature search identified 7395 studies; after applying inclusion and exclusion criteria, 28 studies were identified for critical appraisal: 13 randomized trials and 15 non-randomized studies. Most study interventions (n = 25) focused on surveillance and management of physical effects, including 13 studies that also targeted management of psychosocial effects. Four studies targeted the prevention and surveillance for recurrence and new cancers, and only one study addressed health promotion and disease prevention. Among the 13 randomized studies, 12 had a medium to high risk of bias, and 1 with a low risk of bias. The 15 non-randomized studies included 12 with a high risk and 3 with a medium risk of bias. Common sources of bias included lack of pre-planned sample size and power, lack of blinding of patients or assessors, heterogeneity in population, and attrition with incomplete follow-up. Conclusions: This systematic review and critical appraisal identified gaps in HNC survivorship intervention research targeting under-represented domains of the survivorship framework, and common challenges in study design that introduce risk of bias. To promote quality survivorship care for HNC survivors, scientifically rigorous intervention studies must address broader areas of focus.